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Pharmacokinetics of Shikimic Acid Following Intragastric and Intravenous Administrations in Rats

Authors
  • Noh, Keumhan
  • Back, Hyun-Moon
  • Shin, Beom Soo1
  • Kang, Wonku2
  • 1 School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
  • 2 College of Pharmacy, Chung-Ang University, Seoul 06974, Korea
Type
Published Article
Journal
Pharmaceutics
Publisher
MDPI
Publication Date
Aug 29, 2020
Volume
12
Issue
9
Identifiers
DOI: 10.3390/pharmaceutics12090824
PMID: 32872397
PMCID: PMC7558350
Source
PubMed Central
Keywords
License
Green

Abstract

Shikimic acid, a critical starting material for the semi-total synthesis of oseltamivir to treat and prevent influenza, exerts many pharmacological effects. However, the optimal bioanalytical method has not been adequately defined. We used liquid chromatography-tandem mass spectrometry to quantitate shikimic acid in rat plasma and studied its pharmacokinetics after intragastric and intravenous administration. Plasma was spiked with an internal standard, and the proteins were precipitated with acetonitrile, followed by solvent evaporation and reconstitution of the mobile phase. Shikimic acid was separated on a hydrophilic reverse-phase column and showed a mass transition ([M-H]−) at m/z 173.4→136.6. Shikimic acid exhibited bi-exponential decay after intravenous dosing, with a rapid distribution (5.57 h−1) up to 1 h followed by slow elimination (0.78 h−1). The steady state distribution and clearance volumes were 5.17 and 1.79 L/h/kg, respectively. After intragastric administration, the shikimic acid level peaked at about 3 h, and the material then disappeared mono-exponentially with a half-life of 1.3 h. A double peak phenomenon was observed. The absolute oral bioavailability was about 10% in rats. We explored the relationship between the pharmacokinetics and pharmacodynamics of shikimic acid.

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